When carrying out chemical or biochemical analyses, assays, syntheses or preparations, a large number of separate manipulations are performed on the material(s) or component(s) to be assayed, including measuring, aliquotting, transferring, diluting, mixing, separating, detecting, incubating, etc. Microfluidic technology miniaturizes these manipulations and integrates them so that they can be executed within one or a few microfluidic devices. For example, pioneering microfluidic methods of performing biological assays in microfluidic systems have been developed, such as those described by Parce et al., “High Throughput Screening Assay Systems in Microscale Fluidic Devices” U.S. Pat. No. 5,942,443 and Knapp et al., “Closed Loop Biochemical Analyzers” (WO 98/45481).
Of particular interest in numerous applications utilizing microfluidic devices is the movement/transport of, e.g., samples, reagents, analytes, etc. often in discrete bands (or plugs). For example, in many experimental/assay situations it is desirous to keep plugs of different samples (e.g., a selection of possible enzymatic inhibitors) from diffusing or dispersing into one another as the samples are flowed through various regions of a microfluidic device. This is especially true in high throughput systems where muddying or intermingling of sample plugs can severely decrease throughput efficiency.
Conversely, it is also of interest in the use of microfluidic devices to move/transport fluidic materials (e.g., samples, reagents, analytes, etc.) in such a way as to, e.g., separate multiple materials from within a single plug into various separate plugs and/or to “stretch” a particular sample plug into a longer, and therefore, e.g., less concentrated, length.
The amount/degree of dispersion of samples, etc. in microfluidic devices is influenced by how the samples, etc. are transported through the microfluidic device. Fluidic materials (e.g., in sample plugs) are transported through microfluidic devices in numerous ways using, e.g., electrokinetic flows (electrophoresis or electroosmosis), pressure (e.g., via application of a positive force or via a vacuum), hydrostatic forces, etc. However, various flow regimens used in microfluidic devices can lead to dispersion of plugs of fluid material in the microfluidic elements (e.g., microchannels). For example, pressure driven flow can result in sometimes large amounts of Taylor dispersion of a fluidic material. Additionally, even electroosmotic flow and hydrostatic flow can cause small pressure gradients along a microchannel due to, e.g., mismatch of electroosmotic flow rates, etc. Such can lead to, e.g., dispersion even when fluidic materials are transported via electrokinetic methods.
A welcome addition to the art would be the ability to manipulate the length of sample plugs (e.g., to minimize lengthening [i.e., to keep plugs intact] and/or to maximize lengthening [i.e., to separate mixed samples or to dilute samples]) as the plugs are flowed through a microfluidic device. The current invention describes and provides these and other features by providing new methods, microchannels, and microfluidic devices that meet these and other goals.